A pH-Responsive Charge-Reversal Drug Delivery System with Tumor-Specific Drug Release and ROS Generation for Cancer Therapy

Chen Xu,1,2,* Rijin Song,1,* Pei Lu,1,* Jianchun Chen,2 Yongqiang Zhou,2 Gang Shen,2 Minjun Jiang,2 Wei Zhang1 1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Urology, Affiliated Wujiang Hospita...

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Autores principales:	Xu C, Song R, Lu P, Chen J, Zhou Y, Shen G, Jiang M, Zhang W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	charge-reversal dual-responsive ros generation cancer specific chemotherapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ce3a63e44f9f4fe0bc4bd8a83827312d
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spelling	oai:doaj.org-article:ce3a63e44f9f4fe0bc4bd8a83827312d2021-12-02T06:46:11ZA pH-Responsive Charge-Reversal Drug Delivery System with Tumor-Specific Drug Release and ROS Generation for Cancer Therapy1178-2013https://doaj.org/article/ce3a63e44f9f4fe0bc4bd8a83827312d2020-01-01T00:00:00Zhttps://www.dovepress.com/a-ph-responsive-charge-reversal-drug-delivery-system-with-tumor-specif-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chen Xu,1,2,* Rijin Song,1,* Pei Lu,1,* Jianchun Chen,2 Yongqiang Zhou,2 Gang Shen,2 Minjun Jiang,2 Wei Zhang1 1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Urology, Affiliated Wujiang Hospital of Nantong Univerisity, Suzhou 215200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang Email weizhangsir@126.comMinjun Jiang Email 463161688@qq.comIntroduction: Poor cell uptake and incomplete intracellular drug release are the two major challenges for polymeric prodrug-based drug delivery systems (PPDDSs) in cancer treatment.Methods: Herein, a PPDDS with pH-induced surface charge-reversal and reactive oxygen species (ROS) amplification for ROS-triggered self-accelerating drug release was developed, which was formed by encapsulating a ROS generation agent (vitamin K3 (VK3)) in pH/ROS dual-sensitive polymetric prodrug (PEG-b-P(LL-g-TK-PTX)-(LL-g-DMA)) based micelle nanoparticles (denoted as PVD-NPs).Results: The surface charge of the PVD-NPs can change from negative to positive for enhanced cell uptake in response to tumor extracellular acidity pH. After internalization by cancer cells, PVD-NPs demonstrate dual drug release in response to intracellular ROS-rich conditions. In addition, the released VK3 can produce ROS under the catalysis by NAD(P)H:quinone oxidoreductase-1, which facilitates tumor-specific ROS amplification and drug release selectively in cancer cells to enhance chemotherapy.Conclusion: Both in vitro and in vivo experiments demonstrated that the PVD-NPs showed significant antitumor activity in human prostate cancer.Keywords: charge-reversal, dual-responsive, ROS generation, cancer specific chemotherapyXu CSong RLu PChen JZhou YShen GJiang MZhang WDove Medical Pressarticlecharge-reversaldual-responsiveros generationcancer specific chemotherapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 65-80 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	charge-reversal dual-responsive ros generation cancer specific chemotherapy Medicine (General) R5-920
spellingShingle	charge-reversal dual-responsive ros generation cancer specific chemotherapy Medicine (General) R5-920 Xu C Song R Lu P Chen J Zhou Y Shen G Jiang M Zhang W A pH-Responsive Charge-Reversal Drug Delivery System with Tumor-Specific Drug Release and ROS Generation for Cancer Therapy
description	Chen Xu,1,2,* Rijin Song,1,* Pei Lu,1,* Jianchun Chen,2 Yongqiang Zhou,2 Gang Shen,2 Minjun Jiang,2 Wei Zhang1 1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Urology, Affiliated Wujiang Hospital of Nantong Univerisity, Suzhou 215200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang Email weizhangsir@126.comMinjun Jiang Email 463161688@qq.comIntroduction: Poor cell uptake and incomplete intracellular drug release are the two major challenges for polymeric prodrug-based drug delivery systems (PPDDSs) in cancer treatment.Methods: Herein, a PPDDS with pH-induced surface charge-reversal and reactive oxygen species (ROS) amplification for ROS-triggered self-accelerating drug release was developed, which was formed by encapsulating a ROS generation agent (vitamin K3 (VK3)) in pH/ROS dual-sensitive polymetric prodrug (PEG-b-P(LL-g-TK-PTX)-(LL-g-DMA)) based micelle nanoparticles (denoted as PVD-NPs).Results: The surface charge of the PVD-NPs can change from negative to positive for enhanced cell uptake in response to tumor extracellular acidity pH. After internalization by cancer cells, PVD-NPs demonstrate dual drug release in response to intracellular ROS-rich conditions. In addition, the released VK3 can produce ROS under the catalysis by NAD(P)H:quinone oxidoreductase-1, which facilitates tumor-specific ROS amplification and drug release selectively in cancer cells to enhance chemotherapy.Conclusion: Both in vitro and in vivo experiments demonstrated that the PVD-NPs showed significant antitumor activity in human prostate cancer.Keywords: charge-reversal, dual-responsive, ROS generation, cancer specific chemotherapy
format	article
author	Xu C Song R Lu P Chen J Zhou Y Shen G Jiang M Zhang W
author_facet	Xu C Song R Lu P Chen J Zhou Y Shen G Jiang M Zhang W
author_sort	Xu C
title	A pH-Responsive Charge-Reversal Drug Delivery System with Tumor-Specific Drug Release and ROS Generation for Cancer Therapy
title_short	A pH-Responsive Charge-Reversal Drug Delivery System with Tumor-Specific Drug Release and ROS Generation for Cancer Therapy
title_full	A pH-Responsive Charge-Reversal Drug Delivery System with Tumor-Specific Drug Release and ROS Generation for Cancer Therapy
title_fullStr	A pH-Responsive Charge-Reversal Drug Delivery System with Tumor-Specific Drug Release and ROS Generation for Cancer Therapy
title_full_unstemmed	A pH-Responsive Charge-Reversal Drug Delivery System with Tumor-Specific Drug Release and ROS Generation for Cancer Therapy
title_sort	ph-responsive charge-reversal drug delivery system with tumor-specific drug release and ros generation for cancer therapy
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/ce3a63e44f9f4fe0bc4bd8a83827312d
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A pH-Responsive Charge-Reversal Drug Delivery System with Tumor-Specific Drug Release and ROS Generation for Cancer Therapy

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